Role of Lipids in Spheroidal High Density Lipoproteins

We study the structure and dynamics of spherical high density lipoprotein (HDL) particles through coarse-grained multi-microsecond molecular dynamics simulations. We simulate both a lipid droplet without the apolipoprotein A-I (apoA-I) and the full HDL particle including two apoA-I molecules surrounding the lipid compartment. The present models are the first ones among computational studies where the size and lipid composition of HDL are realistic, corresponding to human serum HDL. We focus on the role of lipids in HDL structure and dynamics. Particular attention is paid to the assembly of lipids and the influence of lipid-protein interactions on HDL properties. We find that the properties of lipids depend significantly on their location in the particle (core, intermediate region, surface). Unlike the hydrophobic core, the intermediate and surface regions are characterized by prominent conformational lipid order. Yet, not only the conformations but also the dynamics of lipids are found to be distinctly different in the different regions of HDL, highlighting the importance of dynamics in considering the functionalization of HDL. The structure of the lipid droplet close to the HDL-water interface is altered by the presence of apoA-Is, with most prominent changes being observed for cholesterol and polar lipids. For cholesterol, slow trafficking between the surface layer and the regimes underneath is observed. The lipid-protein interactions are strongest for cholesterol, in particular its interaction with hydrophobic residues of apoA-I. Our results reveal that not only hydrophobicity but also conformational entropy of the molecules are the driving forces in the formation of HDL structure. The results provide the first detailed structural model for HDL and its dynamics with and without apoA-I, and indicate how the interplay and competition between entropy and detailed interactions may be used in nanoparticle and drug design through self-assembly

Cytotoxin-associated gene antigen-positive strains of Helicobacter pylori

BACKGROUND: Cytotoxin-associated gene antigen (CagA)-positive strains of Helicobacter pylori have previously been associated with acute coronary syndromes. However, the role of CagA-positive strains of Helicobacter pylori in recurring cardiac events after ST-segment elevation myocardial infarction (STEMI) has not yet been assessed. METHODS: We enrolled 181 consecutive patients (155 men, mean age 64±13 years) presenting with STEMI. In all patients, serum levels of IgG anti-CagA were assessed. Levels of IgG anti-hepatitis A virus were also evaluated in all patients in order to exclude the presence of a bystander activation of the immune system. Finally, a previous history of acute coronary syndrome and the rate of major adverse cardiovascular events as a composite of cardiovascular death, recurring myocardial infarction and target lesion revascularisation within 2 years follow-up were evaluated. RESULTS: Anti-CagA IgG seropositive patients presented more frequently with a previous history of acute coronary syndrome compared with seronegative patients (28.3% vs. 14%, P=0.019). Interestingly, no differences were observed between anti-CagA IgG seropositive and anti-CagA IgG seronegative patients concerning the prevalence of anti-hepatitis A virus IgG seropositivity (20% vs. 21.4%, P=0.48). At 2-year follow-up, 40 patients experienced major adverse cardiovascular events. The major adverse cardiovascular event rate was higher in anti-CagA IgG seropositive compared with seronegative patients (hazard ratio 2.25, 95% confidence interval 1.34-2.95, P=0.013), which was confirmed at Cox multivariate analysis (hazard ratio 2.33, 95% confidence interval 1.30-3.14, P=0.009). CONCLUSIONS: CagA-positive strains of Helicobacter pylori seem to be involved in the pathogenesis of recurring acute coronary syndromes, and seropositivity for anti-CagA IgG predicts prognosis after STEMI, possibly due to the increased risk of recurring cardiac events

Electromyographic Analysis of Selected Muscles during Backhand Throw in Ultimate Frisbee

SOUHRN Název: Elektromyografická analýza vybraných svalů během hodu backhand ve hře ultimate frisbee Title: Electromyographic analysis of selected muscles during a backhand throw in ultimate frisbee Cíl práce: Naše práce se zaměřuje na analýzu svalové činnosti během hodu backhand v jedné z nejnovějších kolektivních her- ultimate frisbee. Sleduje míru společné aktivace extenzorů zápěstí - vykonávajících odhození disku a lopatkových svalů (m.trapezius - kraniální a kaudální porce, m.serratus anterior a m.pectoralis major)- dynamických stabilizátorů lopatky. Dále sleduje rozdíly v zapojení svalů během této aktivity ve skupině trénovaných hráčů ultimate. Metoda: Ke snímání aktivity zmíněných svalů jsme použili metodu povrchové elektromyografie. PEMG zachycuje souvislost mezi svalovou aktivitou na akru a kořenovém kloubu horní končetiny během odhodu disku při backhandu. Výsledky: Experiment ukazuje na rozdílnost v aktivaci svalů ve skupině trénovaných hráčů ultimate frisbee, odvíjející se od individuálního vzoru (resp.stylu) pohybového projevu hráče. Při dalším analyzování však vycházejí do popředí dva pohybové modely, odvíjející se od společných znaků či podob získaných vzorů. l.model je charakteristický dominancí m.pectoralis major, ke kterému se ve dvou případech připojuje aktivita m.serratus anterior a v..